Novel anticancer prodrugs of butyric acid. 2
| Autor: | Yael Zimrah, Ester Rabizadeh, Matityahu Shaklai, Ada Rephaeli, Margaretta Ruse, Abraham Nudelman, Adina Aviram |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Melanoma Experimental Antineoplastic Agents Pharmacology Butyric acid Mice chemistry.chemical_compound Leukemia Promyelocytic Acute In vivo Drug Discovery Tumor Cells Cultured medicine Animals Humans Prodrugs Neoplasm Metastasis Cytotoxicity Mice Inbred BALB C Molecular Structure Melanoma Lewis lung carcinoma Cell Differentiation Prodrug medicine.disease In vitro Mice Inbred C57BL Butyrates chemistry Molecular Medicine Female Methyl butyrate Cell Division |
| Zdroj: | Journal of Medicinal Chemistry. 35:687-694 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | The antitumor activity of novel prodrugs butyric acid was examined. The in vitro effect of the compounds on induction of cytodifferentiation and on inhibition of proliferation and clonogenicity showed that (pivaloyloxy)methyl butyrate (1a) (labeled AN-9) was the most active agent. SAR's suggested that its activity stemmed from hydrolytically released butyric acid. In vivo, 1a displayed antitumor activity in B16F0 melanoma primary cancer model, manifested by a significant increase in the life span of the treated animals. Murine lung tumor burden, induced by injection of the highly metastatic melanoma cells (B16F10.9), was decreased by 1a. It also displayed a significant therapeutic activity against spontaneous metastases which were induced by 3LL Lewis lung carcinoma cells. Moreover, 1a has the advantage of low toxicity, with an acute LD50 = 1.36 +/- 0.1 g/kg (n = 5). These results suggest that 1a is a potential antineoplastic agent. |
| Databáze: | OpenAIRE |
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